This cancer information summary provides an overview of the use of Cannabis and its components as a

treatment for people with cancer-related symptoms caused by the disease itself or its treatment.

This summary contains the following key information:

 Cannabis has been used for medicinal purposes for thousands of years.

 By federal law, the possession of Cannabis is illegal in the United States, except within approved
research settings; however, a growing number of states, territories, and the District of Columbia
have enacted laws to legalize its medical use.

 The U.S. Food and Drug Administration has not approved Cannabisas a treatment for cancer or
any other medical condition.

 Chemical components of Cannabis, called cannabinoids, activatespecific receptors throughout

the body to produce pharmacologiceffects, particularly in the central nervous system and
the immune system.

 Commercially available cannabinoids, such as dronabinol and nabilone, are approved drugs for
the treatment of cancer-related side effects.

 Cannabinoids may have benefits in the treatment of cancer-related side effects.

 One study in mice and rats suggested that cannabinoids may have a protective effect
against the development of certain types of tumors.[3] During this 2-year study,
groups of mice and rats were given various doses of THC by gavage. A dose-related
decrease in the incidence of hepatic adenoma tumors and hepatocellular
carcinoma (HCC) was observed in the mice. Decreased incidences of benign
tumors (polyps and adenomas) in other organs(mammary
gland, uterus, pituitary, testis, and pancreas) were also noted in the rats. In another
study, delta-9-THC, delta-8-THC, and cannabinol were found to inhibit the growth of
Lewis lung adenocarcinoma cells in vitro and in vivo .[4] In addition, other tumors
have been shown to be sensitive to cannabinoid-induced growth inhibition.[5-8]
 Cannabinoids may cause antitumor effects by various mechanisms,
including induction of cell death, inhibition of cell growth, and inhibition
of tumor angiogenesis invasion and metastasis.[9-12] Two reviews summarize the
molecular mechanisms of action of cannabinoids as antitumor agents.[13,14]
Cannabinoids appear to kill tumor cells but do not affect their nontransformed
counterparts and may even protect them from cell death. For example, these
compounds have been shown to induce apoptosis in glioma cells in culture and
induce regression of glioma tumors in mice and rats, while they protect normal glial
cells of astroglial and oligodendroglial lineages from apoptosis mediated by the
CB1 receptor.[9]
 The effects of delta-9-THC and a synthetic agonist of the CB2 receptor were
investigated in HCC.[15] Both agents reduced the viability of HCC cells in vitro and
demonstrated antitumor effects in HCC subcutaneous xenografts in nude mice. The
investigations documented that the anti-HCC effects are mediated by way of the CB2
receptor. Similar to findings in glioma cells, the cannabinoids were shown to trigger
cell death through stimulation of an endoplasmic reticulum stress pathway that
activates autophagy and promotes apoptosis. Other investigations have confirmed
that CB1 and CB2 receptors may be potential targets in non-small cell
lung carcinoma [16] and breast cancer.[17]
 An in vitro study of the effect of CBD on programmed cell death in breast cancer cell
linesfound that CBD induced programmed cell death, independent of the CB1, CB2,
or vanilloid receptors. CBD inhibited the survival of both estrogen receptor–
positive and estrogen receptor–negative breast cancer cell lines, inducing apoptosis
in a concentration-dependent manner while having little effect on
nontumorigenic mammary cells.[18] Other studies have also shown the antitumor
effect of cannabinoids (i.e., CBD and THC) in preclinical models of breast
cancer.[19,20]
 CBD has also been demonstrated to exert a chemopreventive effect in a mouse
model of colon cancer.[21] In
this experimental system, azoxymethane increased premalignant and
malignant lesions in the mouse colon. Animals treated with azoxymethane and CBD
concurrently were protected from developing premalignant and malignant lesions.
In in vitro experiments involving colorectal cancer cell lines, the investigators found
that CBD protected DNA from oxidative damage, increased endocannabinoid levels,
and reduced cell proliferation. In a subsequent study, the investigators found that
the antiproliferative effect of CBD was counteracted by selective CB1 but not CB2
receptor antagonists, suggesting an involvement of CB1 receptors.[22]
 Another investigation into the antitumor effects of CBD examined the role of
intercellular adhesion molecule-1 (ICAM-1).[12] ICAM-1 expression has been
reported to be negatively correlated with cancer metastasis. In lung cancer cell lines,
CBD upregulated ICAM-1, leading to decreased cancer cell invasiveness.
 In an in vivo model using severe combined immunodeficient mice, subcutaneous
tumors were generated by inoculating the animals with cells from human non-small
cell lung carcinoma cell lines.[23] Tumor growth was inhibited by 60% in THC-
treated mice compared with vehicle-treated control mice. Tumor specimens
revealed that THC had antiangiogenic and antiproliferative effects. However,
 research with immunocompetentmurine tumor models has
demonstrated immunosuppression and enhanced tumor growth in mice treated
with THC.[24,25]
 In addition, both plant-derived and endogenous cannabinoids have been studied for
anti-inflammatory effects. A mouse study demonstrated that endogenous
cannabinoid system signaling is likely to provide intrinsic protection against
colonic inflammation.[26] As a result, a hypothesis that phytocannabinoids and
endocannabinoids may be useful in the risk reduction and treatment of colorectal
cancer has been developed.[27-30]
 CBD may also enhance uptake of cytotoxic drugs into malignant cells. Activation of
the transient receptor potential vanilloid type 2 (TRPV2) has been shown to inhibit
proliferation of human glioblastoma multiforme cells and overcome resistance to
the chemotherapy agent carmustine.[31] One study showed that coadministration
of THC and CBD over single-agent usage had greater antiproliferative activity in
an in vitro study with multiple human glioblastoma multiforme cell lines.[32] In
an in vitro model, CBD increased TRPV2 activation and increased uptake of cytotoxic
drugs, leading to apoptosis of glioma cells without affecting normal
human astrocytes. This suggests that coadministration of CBD with cytotoxic agents
may increase drug uptake and potentiate cell death in human glioma cells. Also, CBD
together with THC may enhance the antitumor activity of classic chemotherapeutic
drugs such as temozolomide in some mouse models of cancer.[13,33]

 Antiemetic Effects
 Preclinical research suggests that emetic circuitry is tonically controlled by
endocannabinoids. The antiemetic action of cannabinoids is believed to be mediated
via interaction with the 5-hydroxytryptamine 3 (5-HT3) receptor. CB1 receptors
and 5-HT3 receptors are colocalized on gamma-aminobutyric acid (GABA)-ergic
neurons, where they have opposite effects on GABA release.[34] There also may be
direct inhibition of 5-HT3 gated ion currents through non–CB1 receptor pathways.
CB1 receptor antagonists have been shown to elicit emesis in the least shrew that is
reversed by cannabinoid agonists.[35] The involvement of CB1 receptor in emesis
prevention has been shown by the ability of CB1 antagonists to reverse the effects of
THC and other synthetic cannabinoid CB1 agonists in suppressing vomiting caused
by cisplatin in the house musk shrew and lithiumchloride in the least shrew. In the
latter model, CBD was also shown to be efficacious.[36,37]
 Appetite Stimulation
 Many animal studies have previously demonstrated that delta-9-THC and other
cannabinoids have a stimulatory effect on appetite and increase food intake. It is
believed that the endogenous cannabinoid system may serve as a regulator of
feeding behavior. The endogenous cannabinoid anandamide potently enhances
appetite in mice.[38] Moreover, CB1 receptors in the hypothalamus may be involved
in the motivational or reward aspects of eating.[39]

 Analgesia
 Understanding the mechanism of cannabinoid-induced analgesia has been increased
through the study of cannabinoid receptors, endocannabinoids, and synthetic
agonists and antagonists. Cannabinoids produce analgesia through supraspinal,
spinal, and peripheral modes of action, acting on both ascending and descending
pain pathways.[40] The CB1 receptor is found in both the central nervous
system (CNS) and in peripheral nerveterminals. Similar to opioid receptors,
increased levels of the CB1 receptor are found in regions of the brain that regulate
nociceptive processing.[41] CB2 receptors, located predominantly in
peripheral tissue, exist at very low levels in the CNS. With the development of
receptor-specific antagonists, additional information about the roles of the
receptors and endogenous cannabinoids in the modulation of pain has been
obtained.[42,43]
 Cannabinoids may also contribute to pain modulation through an anti-inflammatory
mechanism; a CB2 effect with cannabinoids acting on mast cell receptors to
attenuate the release of inflammatory agents, such as histamine and serotonin, and
on keratinocytes to enhance the release of analgesic opioids has been described.[44-
46] One study reported that the efficacy of synthetic CB1- and CB2-receptor agonists
were comparable with the efficacy of morphine in a murine model of tumor
pain.[47]
 Cannabinoids have been shown to prevent chemotherapy-induced neuropathy in
animal models exposed to paclitaxel, vincristine, or cisplatin.[48-50]

 Anxiety and Sleep

 The endocannabinoid system is believed to be centrally involved in the regulation of
mood and the extinction of aversive memories. Animal studies have shown CBD to
have anxiolytic properties. It was shown in rats that these anxiolytic properties are
 mediated through unknown mechanisms.[51] Anxiolytic effects of CBD have been
shown in several animal models.[52,53]
 The endocannabinoid system has also been shown to play a key role in the
modulation of the sleep-waking cycle in rats.[54,55]
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http://scienceblog.cancerresearchuk.org/2012/07/25/cannabis-cannabinoids-and-cancer-the-evidence-
so-far/